The following is a summary of “Depressive Syndromes in Men With Hypogonadism in the TRAVERSE Trial: Response to Testosterone-Replacement Therapy,” published in the July 2024 issue of Endocrinology by Bhasin, et al.

The impact of testosterone on depressive symptoms in men with hypogonadism is not fully understood, particularly regarding how testosterone-replacement therapy (TRT) affects depressive symptoms in this population. 

For a study, researchers sought to evaluate the effects of TRT on depressive symptoms in men with hypogonadism, both with and without depressive symptoms, who were enrolled in the TRAVERSE cardiovascular safety trial.

A randomized, placebo-controlled, double-blind trial was conducted at 316 sites. Participants included men aged 45 to 80 years with 2 fasting testosterone levels below 300 ng/dL, at least 1 hypogonadal symptom, cardiovascular disease (CVD), or increased CVD risk. They analyzed 3 subgroups that were men with rigorously defined late-life onset low-grade persistent depressive disorder (LG-PDD); all men with significant depressive symptoms (Patient Health Questionnaire-9 Score >4); and all men randomly assigned to the trial. Participants received either 1.62% transdermal testosterone or placebo gel. Outcome measures included proportions of participants meeting LG-PDD criteria or having significant depressive symptoms, and changes in mood, energy, sleep quality, and cognition between testosterone and placebo groups within the subgroups.

Of 5,204 participants, 2,643 (50.8%) had significant depressive symptoms, but only 49 (1.5%) met the rigorous criteria for LG-PDD. Among men with LG-PDD, no significant differences were found between the TRT and placebo groups, potentially due to low statistical power. In contrast, among men with significant depressive symptoms (n= 2,643) and all participants (n= 5,204), TRT was associated with modest but statistically significant improvements in mood and energy, though it did not significantly affect cognition or sleep quality.

Depressive symptoms were prevalent in middle-aged and older men with hypogonadism, though LG-PDD is rare. TRT is linked to minor improvements in mood and energy in men with hypogonadism, regardless of the presence of significant depressive symptoms, but does not significantly impact cognition or sleep quality.

Reference: academic.oup.com/jcem/article-abstract/109/7/1814/7516050